Friday Hope: Vanillin: Quelling Viral Oncogenic Signaling Pathways and Binding Spike/mPRO

The ubiquitous flavor extract is anything but “plain vanilla” This mixture of ~ 200 compounds from an orchid provides a plethora of benefits.

Given that SARS-CoV-2 and its Spike Protein have been proven very adept at activating oncogenic signaling pathways, I have been looking to Nature to provide us with solutions. And, as always, Nature does not disappoint. Among the first flavors we remember from childhood (with fondness, anyway) are Vanilla and Chocolate, and how everyone always seems to have a strong preference for one or the other. It turns out, both are quite amazing. Today, we will focus on Vanilla and its many benefits. 

First, other than being a universally recognized flavor, what exactly is Vanilla? 

Vanilla is arguably the world’s most popular flavour and is derived from mature pods of the orchid Vanilla planifolia. It constitutes one of the most preferred flavours and fragrance ingredients in ice-creams, confectioneries, milk products, perfumes, pharmaceuticals, liqueur and other cordial industries, thereby forming a whopping multimillion-dollar market (Gallage and Møller 2018). For centuries vanilla flavour remained classified for the rest of the world since it was ascribed as a flavour of nobility by Aztecs and pre-Columbian Mayas. It was in 1519 that vanilla was exposed to the world with the Spanish invasion of the Aztecs. It was transported to Europe and subsequent development of hand pollination techniques led to its expansion to other parts of the world (Teoh 2019). Today, Madagascar is the largest producer of natural vanilla with 75% of world production followed by Indonesia, China, Mexico, and Papua New Guinea. Vanilla is a mixture of ~ 200 compounds; however, it’s characteristic flavour and fragrance comes mainly from the molecule vanillin (Gallage and Møller 2018). 

Vanillin: a review on the therapeutic prospects of a popular flavouring molecule 
https://link.springer.com/article/10.1007/s13596-020-00531-w 

This “mixture of ~200 compounds” has many uses. One of the most outstanding is its ability to quell oncogenic signaling pathways. Especially those activated by the Spike Protein. Please see my previous post detailing how SARS-CoV-2 and its Spike Protein activate oncogenic signaling pathways. 

Reports that implicate vanillin in mediation of DNA damage and antimutagenic potential have encouraged researchers to evaluate the anticancer effects at cellular and molecular levels (Bezerra et al. 2016). Vanillin (1000 µg/mL) inhibited the proliferation of HT-29 cells (Colon cancer cells) where significant cell arrest occurred during the G0/G1 phase and an increase in apoptotic cells in sub-G0 phase was observed (Ramadoss and Sivalingam 2019). Further, a derivative of vanillin, 4-(1H-imidazo [4,5-f] [1,10]-phenanthrolin-2-yl)-2-methoxyphenol (IPM711) showed growth inhibition, invasion and migration of HT-29 and HCT116 cells by binding to a Wnt/β-catenin signalling receptor (Ma et al. 2019). In this study, vanillin down-regulated proteasome genes in colon tissues and significantly suppressed proteasome activity. Furthermore, at 10 mM it hindered the mitogen-activated protein kinase (MAPK) phosphorylation, reducing the number of granulocytes in colon tissue, proliferating cells and p65-positive cells. Amelioration of cancerous activity by vanillin might be associated with downregulation of the proteasome genes, MAPK pathway and nuclear factor-κB (Li et al. 2018). A vanillin derivative VND3207 has shown a strong radio-protective effect in radiation-induced intestinal injury in mice (Li et al. 2020). VND3207 was found to alleviate the radiation injury in human lymphoblastoid cells by enhancing the expression of the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) which is an essential part of DNA double-strand break repair mechanism. 

Vanillin: a review on the therapeutic prospects of a popular flavouring molecule 
https://link.springer.com/article/10.1007/s13596-020-00531-w 

Remarkable. Vanillin inhibits MAPK, Wnt/β-catenin and Nf-KB oncogenic pathways. It also protects from radiation-induced injury and assists in DNA repair.  

Additionally, Vanillin is neuroprotective and inhibits amyloid aggregation and ROS – two other adverse Spike effects. 

Neuroprotective effects and mechanisms of vanillin. Vanillin exerts multiple different protective effects on various neurological conditions. Main neuroprotective effects and mechanisms of vanillin on chronic neurodegenerative diseases and neuropathophysiological conditions are summarized in panel (A). Molecular signaling pathways involved in vanillin anti-inflammatory, anti-oxidant, and anti-apoptotic activity are outlined in panel (B). 

Overview of the Role of Vanillin in Neurodegenerative Diseases and Neuropathophysiological Conditions 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9915872/ 

It is also worth noting that Vanillin shows promise in inhibiting the Spike and the mPRO of SARS-CoV-2.  

Recently reports on SARS-CoV-2 suggests that vanillin has moderate affinity towards spike protein and main protease. Thus, further studies should be undertaken to enhance the inhibitory potential of vanillin and its derivative on SARS-CoV-2. Altogether, such findings suggest that vanillin and its derivatives can become suitable starting compounds for further lead optimization as NA inhibitors. 

Vanillin: a review on the therapeutic prospects of a popular flavouring molecule 
https://link.springer.com/article/10.1007/s13596-020-00531-w 

I will continue to search for natural solutions to oncogenic pathway activation. As always, I am thankful every day for your support, readership and dialog. It is a beautiful early Autumn day here in Vermont. I wish light, beauty and warmth to all this September weekend. 

Oh! I am a huge fan of Vanilla. I think Snoopy summed it up best: 

Charlie Brown: I don’t understand you. You always order Vanilla. They have forty other flavors, and yet you always order Vanilla.  

Snoopy: I’m a purist.